Simultaneous analysis of the expression of 14 genes with individual prognostic value in myelodysplastic syndrome patients at diagnosis: WT1 detection in peripheral blood adversely affects survival

Santamaría, Carlos; Ramos, Fernando; Puig, Noemí; Barragán, Eva; Paz, Raquel de; Pedro, Carme; Insunza, Andrés; Tormo, Mar; Cañizo, Consuelo del; Díez-Campelo, María; Xicoy, Blanca; Salido, Eduardo; Real, Javier Sánchez del; Hernández, Montserrat; Chillón, Carmen; Sanz, Guillermo; Miguel, Jesús F. San; González, Marcos

doi:10.1007/s00277-012-1538-7

Cited by 12 publications

(11 citation statements)

References 39 publications

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“…According to these data, the current study provides evidence on the role of some genes not previously described in hematological malignancies, on the outcome of patients with MDS and AML, in terms of survival and probability of response to new therapies. Future incorporation of these and other markers previously identified [43][44][45] in this otherwise very heterogeneous group of patients might help in driving treatment decisions and prognosis refinement. However, external validation and additional functional studies on the role of these genes in the pathogenesis of MDS and AML are needed.…”

Section: Discussionmentioning

confidence: 94%

Overexpression of GYS1, MIF, and MYC Is Associated With Adverse Outcome and Poor Response to Azacitidine in Myelodysplastic Syndromes and Acute Myeloid Leukemia

Falantes

Trujillo

Piruat

et al. 2015

Clinical Lymphoma Myeloma and Leukemia

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Section: Discussionmentioning

confidence: 94%

Overexpression of GYS1, MIF, and MYC Is Associated With Adverse Outcome and Poor Response to Azacitidine in Myelodysplastic Syndromes and Acute Myeloid Leukemia

Falantes

Trujillo

Piruat

et al. 2015

Clinical Lymphoma Myeloma and Leukemia

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“…Scopim-Ribeiro et al (2015) [22] included patients with both de novo AML and MDS, however, only patients with MDS were included in the meta-analysis. The median age in the eight studies [12, 15, 16, 22, 23, 25–27] was older than 60 years old, the median age was younger than 60 years old in four studies [20, 21, 24, 28] and the median age was not available in the other two studies [29, 30]. Patients in 10 eligible studies [12, 14, 20–27] were classified by WHO criteria, patients in 3 studies [28–30] were classified by FAB criteria and patients in KOSMIIDER et al (2009) [16] were classified by both WHO and FAB criteria.…”

Section: Resultsmentioning

confidence: 99%

Prognostic role of TET2 deficiency in myelodysplastic syndromes: A meta-analysis

Lin

Cheng

et al. 2017

Oncotarget

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Tet methylcytosine dioxygenase2 gene (TET2) is one of the most frequently mutated gene in myeloid neoplasm, but the prognostic role of TET2 aberrations in myelodysplastic syndromes (MDS) remains unclear. Therefore, we performed a meta-analysis. Fourteen eligible studies with 1983 patients were included in this meta-analysis. Among these, 2 studies evaluated the impact that the TET2 expression level had on the prognosis. The combined hazard ratios (HR) estimated for overall survival (OS) was 1.00 (95%CI: 0.74 to 1.37; p=0.989) when comparing those with TET2 mutations with those without. Among the patients treated with hypomethylating agents (HMAs) or hematopoietic stem cell transplantation (HSCT), the pooled HR for OS was 1.02 (95% CI: 0.77-1.35, p=0.89) and 1.54 (95%CI: 0.69 to 3.44; p=0.29), respectively. We also conducted an analysis of the response rate to HMAs, and the OR was 1.73 (95%CI: 1.11 to 2.70; p=0.016). Additionally, subgroup analyses showed the pooled HR for OS was 0.93(95%CI: 0.44 to 1.98; P=0.849) in WHO-classified CMML patients and 1.02(95%CI: 1.02 to 3.46; p=0.042) in studies evaluated TET2 expression level. The analysis suggested TET2 mutations had no significant prognostic value on MDS. However, the response rates to HMAs were significantly different between those with and without TET2 mutations, and the low expression level of TET2 gene was significantly associated with a poor OS in MDS patients.

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“…[55][56][57] IEX-1 downregulation has been suggested to be linked to the high level of apoptosis observed in these patients. Our results showing that Iex-1…”

Section: Kitmentioning

confidence: 99%

Thrombopoietin promotes NHEJ DNA repair in hematopoietic stem cells through specific activation of Erk and NF-κB pathways and their target, IEX-1

Laval

Pawlikowska

Barbieri

et al. 2014

Blood

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Key Points• TPO specifically activates Erk and NF-kB pathways in hematopoietic stem and progenitor cells.• Erk and NF-kB cooperate to trigger their common target, Iex-1, and DNA-PKdependent NHEJ activation in HSPCs upon irradiation.Loss of hematopoietic stem cell (HSC) function and increased risk of developing hematopoietic malignancies are severe and concerning complications of anticancer radiotherapy and chemotherapy. We have previously shown that thrombopoietin (TPO), a critical HSC regulator, ensures HSC chromosomal integrity and function in response to g-irradiation by regulating their DNA-damage response. TPO directly affects the double-strand break (DSB) repair machinery through increased DNA-protein kinase (DNA-PK) phosphorylation and nonhomologous end-joining (NHEJ) repair efficiency and fidelity. This effect is not shared by other HSC growth factors, suggesting that TPO triggers a specific signal in HSCs facilitating DNA-PK activation upon DNA damage. The discovery of these unique signaling pathways will provide a means of enhancing TPO-desirable effects on HSCs and improving the safety of anticancer DNA agents. We show here that TPO specifically triggers Erk and nuclear factor kB (NF-kB) pathways in mouse hematopoietic stem and progenitor cells (HSPCs). Both of these pathways are required for a TPO-mediated increase in DSB repair. They cooperate to induce and activate the early stress-response gene, Iex-1 (ier3), upon DNA damage. Iex-1 forms a complex with pERK and the catalytic subunit of DNA-PK, which is necessary and sufficient to promote TPO-increased DNA-PK activation and NHEJ DSB repair in both mouse and human HSPCs. (Blood. 2014;123(4):509-519)

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Simultaneous analysis of the expression of 14 genes with individual prognostic value in myelodysplastic syndrome patients at diagnosis: WT1 detection in peripheral blood adversely affects survival

Cited by 12 publications

References 39 publications

Overexpression of GYS1, MIF, and MYC Is Associated With Adverse Outcome and Poor Response to Azacitidine in Myelodysplastic Syndromes and Acute Myeloid Leukemia

Overexpression of GYS1, MIF, and MYC Is Associated With Adverse Outcome and Poor Response to Azacitidine in Myelodysplastic Syndromes and Acute Myeloid Leukemia

Prognostic role of TET2 deficiency in myelodysplastic syndromes: A meta-analysis

Thrombopoietin promotes NHEJ DNA repair in hematopoietic stem cells through specific activation of Erk and NF-κB pathways and their target, IEX-1

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